Leukopoiesis

The doctor started by revising some of the previous lecture: Average WBC (count/mm³): Neutrophils: 5,400 (60%) Eosinophils: 275 (3%) Basophils: 35 (0.5-1%) Lymphocytes: 2750 (34%) Monocytes: 540 (4%)  Therefore, neutrophils are the most abundant followed by lymphocytes, monocytes, eosinophils and basophils, respectively. (NLMEB)  According to the doctor, neutrophils are not always the most abundant WBCs, sometimes there can be more lymphocytes than neutrophils, but this is very rare.  The lymphocytes we count make up only 50% of the total number of lymphocytes as the remainder adhere to the inner surfaces of the blood vessels. These adhering lymphocytes are referred to as the marginal pool and they are only released in some conditions like hemorrhage. Leukopoiesis Leukopoiesis: the production of white blood cells. Duration: The duration required for the production of WBCs via leukopoiesis is 6 days, which is the same amount of time taken for the production of RBCs, but WBCs remain in the bone marrow for 6 more days after they're produced so that they can be "computerized" before being released to the circulation.  What is "computerization" and why it's needed? In books it's written that those additional 6 days is for WBCs to mature. But actually, it's for them to be activated (i.e. computerized) because they need to be activated to function, so if you take WBCs from bone marrow immediately it won't function. This is for all WBCs but most specifically lymphocytes. Location: All the WBCs are only produced in the bone marrow except the lymphocytes which are produced in both the bone marrow and the lymphoid tissues (e.g. lymph nodes, spleen, and thymus). Therefore, if there's a problem in the bone marrow all WBCs will decrease except lymphocytes (they will decrease but not as much as other WBCs). 1|Page Content of WBCs: WBCs play a very important role in the immunity; therefore they contain several enzymes to kill microbes, but Basophils contain both enzymes and chemicals (e.g. hormones, heparin, histamine and serotonin). WBCs storage: We need high storage of WBCs, so there are 2 storages: Bone marrow & the marginal pool located on the lining of blood vessels. - Normally, 75% of the cells in the bone marrow belong to the WBCs family, this is most likely due to their short half-lives. Process: Leukopoiesis is the most complicated process in the body, because: - Many chemicals (i.e. regulators) are involved in the production of WBCs such as IL-1 and Factor III. - These chemicals affect many cell lineages. - Each stage is affected by many factors. - One chemical can be produced by more than 1 source. - In each stage there are many cells produced, and there is an overlap in the function of the regulating chemicals. - The mother stem cell is affected by many factors to determine which pathway it follows, so if any of them is deficient then the mother cell won't function probably. From this idea the stem cell therapy came. This therapy depends on that taking a cell and transplant it in an organ, that cell will produce the same cells similar to that of the organ. And as it's known, the most capable cells to produce new cells are the placental cells. Granulocyte Macrophage Colony Stimulating Factor (GM-CSF): -Culturing a single cell with giving it this factor results in the production of a colony of cells (many cells in groups) -This factor affects several cells in the blood cell production lineages. 2|Page A single type of stem cells produces many different cell types including RBCs and platelets. So, we’ll see shortly that when there is a problem in the production of the WBCs, the RBCs and the platelets are also affected (e.g. in leukemia at the end of the sheet 😊). All WBCs have these 4 characteristics (But with variant degrees): 1. Diapedesis is the process by which WBCs pass through walls of capillaries to enter tissues in order to perform their functions. 2. Amoeboid motion is the motion used by WBCs to move in capillaries & tissues. 3. Chemotaxis is a process in which WBCs are repelled from the normal intact areas and attracted to the infected/injured areas. 4. Phagocytosis is the ability to engulf, digest and kill bacteria and products of cells. WBCs can also engulf dead cells by phagocytosis. Almost all of the WBCs have this feature. These characteristics are clearly seen in neutrophils, and least seen in basophils because basophils have mainly the feature of chemicals production. Disorders 1. High WBC count: In all infections whether it's viral or bacterial, all WBC types increase but with variant degrees. There are specific things to be noted for each cell type: - Neutrophils: Increase mainly in bacterial infections. - Lymphocytes: Increase drastically in viral infections - Monocytes: Increase in fungal or viral infections, but mostly in tuberculosis or similar infections. - Eosinophils: Increase in parasitic and allergic reactions. Allergy is very specific to eosinophils, so that if a patient comes with a suspected allergy the doctor is supposed to ask for an eosinophil count test. - Basophil: Increase in allergic reactions. 2. Low WBC count: In contrast with high white blood cell count, there are some cases in which specific kinds of leukocytes decrease in number leading to a low white blood cell count. 3|Page • Neutrophils decrease in number in: abcd- Prolonged exposure to radiations. Drug toxicity. Vitamin B12 deficiency. Systemic lupus erythematous (SLE). • Lymphocytes decrease in: a- Prolonged illness. b- Immunosuppression. c- Treatment with cortisol. • Monocytes decrease in: a- Bone marrow failure. b- Cortisol treatment. • Eosinophils decrease in: a- Drug toxicity. b- Prolonged stress. • Basophils decrease in: a- Pregnancy. b- Hyperthyroidism. c- Ovulation and stress. Note: Black-skinned people tend to have leukopenia, even at the dead sea level. The doctor talked about a study he previously carried; I don’t know if the following info is required: It is well known that hypoxia causes an increase in the RBC count, so the doctor and his colleagues wanted to see how things go with hyperoxia (e.g. at the dead sea level), and they found that those who were living in areas with hyperoxia often had low RBC count. Then they decided to study the WBCs too, using samples from school students, they found that people living in those areas tend to have low WBC count too, but then, when they compared their results to the references, they figured out that it had to do more with the race (black- skinned people) than with the place/hyperoxia. The doctor said that in their study they noticed high number of monocytes in students with parasitic infections. Sometimes the low WBC count runs in families rather than whole races. 4|Page 3. Leukemia: When leukocytosis (increase in the WBC count) occurs and the cause is identified and then removed, the count is supposed to return back to normal, if it doesn’t return to the normal range then this condition is called “Leukemia” which is a tumor condition (an uncontrolled production of the WBCs) in which the number increases drastically. Usually it's late diagnosed and the patient may die, and it's rarely early discovered. A. Causes of Leukemia: The causes of most leukemia types are unknown but there're certain specific factors have been identified such as: chronic exposure to radiations, chemicals or viruses, environment and genetic factors. B. Leukemia symptoms: Symptoms are similar to flu which are: bone pain, paleness, tendency to bleed, frequent infections and anemia. C. Types of Leukemia: It's divided into: 1- Acute or chronic depending on the disease presentation.  Acute Leukemia: Occurs suddenly, usually in children. Sometimes the acute form happens after the chronic one.  Chronic Leukemia: It's the most common form in adults as it develops and comes slowly without warning (so it has enough time in adults compared to children) and sometimes the leukemia may take years to develop symptoms or to be detected as most cases are discovered during routine examination and even after agents in the blood are detected. 2- Myelocytic or lymphocytic depending on the site.  Myelocytic Leukemia: in bone marrow.  Lymphocytic Leukemia: in lymphoid tissue. 5|Page Usually leukemia affects all the WBC types, but as WBCs originate either from the lymphoid lineage or the myeloid lineage, sometimes leukemia can occur in one of the two pathways so we have myelocytic leukemia (e.g. in neutrophils, basophils, eosinophils or monocytes only) and lymphocytic leukemia (e.g. in lymphocytes), other times leukemia affects all the WBC types. D. Leukemia cells morphology:  The leukemia cells are bizarre, highly undifferentiated and not identical with any of the normal WBCs therefor they don't function  Usually the more undifferentiated the cells the more acute is the leukemia, but with some of the highly differentiated cells the process can be quite chronic and span a very long duration (e.g. 10-20 years).  Leukemia cells, especially those that are highly undifferentiated, are usually non-functional, which is why the patients get easily infected. E. The effects of leukemia on the body: - The basic effect is metastatic growth of leukemia cells in abnormal areas. - Leukemia cells in the bone marrow invade the surrounding bone and the neighboring tissues. - Leukemia often metastasizes to spleen, lymph nodes, liver and vascular regions. In each of these areas the repeatedly growing cells invade the surrounding tissue neutralizing the metabolic elements of the tissue consequently causing tissue destruction. So, leukemia is curable before wide- spread metastasis. - Development of infections. - Severe anemia (remember that when we discussed leukopoiesis, we said that diseases affecting the production of WBCs also affect the production of RBCs and platelets). - Bleeding tendency caused by thrombocytopenia (low platelet count). - The most important effect of leukemia is the continuous use of the nutrients, vitamins and metabolic substrates by the growing cancerous cells. Consequently, the energy of the patient is greatly depleted, rapid deterioration of the normal protein tissues of the body. If this metabolic starvation stayed long enough, it'll be sufficient to cause death. 6|Page